N-环丙基-11-(3-羟基-5-戊基苯氧基)十一碳酰胺 | 869376-63-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: N-环丙基-11-(3-羟基-5-戊基苯氧基)十一碳酰胺
• 英文名称: CB 25
• 英文别名: 11-(3-hydroxy-5-pentylphenoxy)undecanoic acid cyclopropylamide；N-cyclopropyl-11-(3-hydroxy-5-pentylphenoxy)undecanamide；CB25；11-(3-hydroxy-5-pentyl-phenoxy)-undecanoic acid cyclopropylamide
• CAS: 869376-63-6
• 化学式: C₂₅H₄₁NO₃
• 分子量: 403.605
• InChiKey: XFHZHCKWTBGPFD-UHFFFAOYSA-N

物化性质

• 熔点：
  70.7 °C(Solv: chloroform (67-66-3); methanol (67-56-1))
• 沸点：
  594.7±30.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL；乙醇：50mg/mL；乙醇:PBS (pH 7.2) (1:2): 0.3 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  29
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，置于干燥处

制备方法与用途

CB-25是CB1大麻素受体的配体，作为一种部分激动剂。它能够增强HY-15371诱导的癌症细胞中cAMP的生成，但在hCB1-CHO细胞中并无此效果。

反应信息

• 作为反应物：
  描述：

  N-环丙基-11-(3-羟基-5-戊基苯氧基)十一碳酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以55%的产率得到3-(11-(cyclopropylamino)undecyloxy)-5-pentylphenol
  参考文献：
  名称：

  Structure–affinity relationships and pharmacological characterization of new alkyl-resorcinol cannabinoid receptor ligands: Identification of a dual cannabinoid receptor/TRPA1 channel agonist

  摘要：

  In our ongoing program aimed at deeply investigating the endocannabinoid system (ES), a set of new alkyl-resorcinol derivatives was prepared focusing on the nature and the importance of the carboxamide functionality. Binding studies on CB1 and CB2 receptors, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) showed that some of the newly developed compounds behaved as very potent cannabinoid receptor ligands (Ki in the nanomolar range) while, however, none of them was able to inhibit MAGL and/or FAAH. Derivative 11 was a potent CB1 and CB2 ligand, with Ki values similar to WIN 55,212, exhibiting a CB1 and CB2 agonist profile in vitro. In the formalin test of peripheral acute and inflammatory pain in mice, this compound showed a weak and delayed antinociceptive effect against the second phase of the nocifensive response, exhibiting, interestingly, a quite potent transient receptor potential ankyrin type-1 (TRPA1) channel agonist activity. Moreover, derivative 14, characterized by lower affinity but higher CB2 selectivity than 11, proved to behave as a weak CB2 competitive inverse agonist.

  DOI：

  10.1016/j.bmc.2014.07.006
• 作为产物：
  描述：

  3,5-二羟基戊苯 在 potassium fluoride 、 sodium hydroxide 、 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 、 potassium carbonate 、 1-羟基苯并三唑 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 27.5h， 生成 N-环丙基-11-(3-羟基-5-戊基苯氧基)十一碳酰胺
  参考文献：
  名称：

  大麻素受体新有效配体的设计，合成和结合研究。

  摘要：

  尽管它们的化学结构不同，delta9-四氢大麻酚（THC）和阿南酰胺（AEA）具有共同的药理特性。这项研究旨在寻找克服AEA及其类似物不稳定性的新型大麻素受体配体。为此，我们计划合成一系列化合物，这些化合物既保留了植物大麻素的刚性结构，又保留了类似于anandamide的柔性部分。对CB1和CB2受体，阿南酰胺膜转运蛋白（AMT）和脂肪酸酰胺水解酶（FAAH）的结合研究表明，一些新开发的化合物对大麻素CB1和CB2受体具有很高的亲和力和特异性。化合物25是有效的CB1和CB2配体，其亲和常数明显低于AEA，与WIN 55-212类似，化合物52是有效的CB2配体，尽管化合物对CB1受体的选择性不是很高，但化合物43是CB2配体，其选择性比CB1受体至少高26倍。化合物25在循环AMP功能试验中对CB1受体起反向激动剂的作用。

  DOI：

  10.1021/jm0501533

文献信息

• POTENT AND SELECTIVE LIGANDS OF CANNABINOID RECEPTORS
  申请人：Brizzi Antonella

  公开号：US20090043129A1

  公开（公告）日：2009-02-12

  The present invention relates to high affinity compounds, able to bind CB 1 and CB 2 endocannabinoid receptors. The compounds of the invention find particular application as agents for pain therapy and/or anti-inflammatory and/or anti-stress and/or anti-oxidising and/or hypotensive and/or immune suppressive therapy and/or anti-spastic activity in multiple sclerosis and/or anti-cancer.

  本发明涉及高亲和力化合物，能够结合CB1和CB2内源性大麻素受体。本发明的化合物在疼痛治疗和/或抗炎症和/或抗压力和/或抗氧化和/或降压和/或免疫抑制治疗和/或多发性硬化症的抗痉挛活性和/或抗癌症方面具有特殊应用。
• NEW POTENT AND SELECTIVE LIGANDS OF CANNABINOID RECEPTORS
  申请人：Universita' Degli Studi di Siena

  公开号：EP1846364A1

  公开（公告）日：2007-10-24
• [EN] NEW POTENT AND SELECTIVE LIGANDS OF CANNABINOID RECEPTORS<br/>[FR] NOUVEAUX LIGANDS PUISSANTS ET SELECTIFS DES RECEPTEURS DES CANNABINOIDES
  申请人：UNIV SIENA

  公开号：WO2006080040A1

  公开（公告）日：2006-08-03

  [EN] The present invention relates to high affinity compounds, able to bind CB₁ and CB₂ endocannabinoid receptors. The compounds of the invention find particular application as agents for pain therapy and/or anti-inflammatory and/or anti-stress and/or anti-oxidising and/or hypotensive and/or immune suppressive therapy and/or anti-spastic activity in multiple sclerosis and/or anti-cancer.
  [FR] Composés à haute affinité, capables de se lier aux récepteurs CB₁ et CB₂ des endocannabinoïdes. Les composés selon la présente invention trouvent une application particulière en tant qu'agents pour la thérapie de la douleur et / ou pour la thérapie anti-inflammatoire et / ou anti-stress et ou antioxydante et / ou de l'hypotension et / ou de l'immunosuppression et / ou de l'activité antispasmodique dans la sclérose en plaques et / ou du cancer.
• Structure–affinity relationships and pharmacological characterization of new alkyl-resorcinol cannabinoid receptor ligands: Identification of a dual cannabinoid receptor/TRPA1 channel agonist
  作者：Antonella Brizzi、Francesca Aiello、Pietro Marini、Maria Grazia Cascio、Federico Corelli、Vittorio Brizzi、Luciano De Petrocellis、Alessia Ligresti、Livio Luongo、Stefania Lamponi、Sabatino Maione、Roger G. Pertwee、Vincenzo Di Marzo

  DOI：10.1016/j.bmc.2014.07.006

  日期：2014.9

  In our ongoing program aimed at deeply investigating the endocannabinoid system (ES), a set of new alkyl-resorcinol derivatives was prepared focusing on the nature and the importance of the carboxamide functionality. Binding studies on CB1 and CB2 receptors, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) showed that some of the newly developed compounds behaved as very potent cannabinoid receptor ligands (Ki in the nanomolar range) while, however, none of them was able to inhibit MAGL and/or FAAH. Derivative 11 was a potent CB1 and CB2 ligand, with Ki values similar to WIN 55,212, exhibiting a CB1 and CB2 agonist profile in vitro. In the formalin test of peripheral acute and inflammatory pain in mice, this compound showed a weak and delayed antinociceptive effect against the second phase of the nocifensive response, exhibiting, interestingly, a quite potent transient receptor potential ankyrin type-1 (TRPA1) channel agonist activity. Moreover, derivative 14, characterized by lower affinity but higher CB2 selectivity than 11, proved to behave as a weak CB2 competitive inverse agonist.
• Design, Synthesis, and Binding Studies of New Potent Ligands of Cannabinoid Receptors
  作者：Antonella Brizzi、Vittorio Brizzi、Maria Grazia Cascio、Tiziana Bisogno、Rossella Sirianni、Vincenzo Di Marzo

  DOI：10.1021/jm0501533

  日期：2005.11.1

  developed compounds have high affinity and specificity for cannabinoid CB1 and CB2 receptors. Compound 25 is a potent CB1 and CB2 ligand, with affinity constants significantly lower than AEA and similar to WIN 55-212, compound 52 is a potent CB2 ligand, although not very selective over CB1 receptors, and compound 43 is CB2 ligand, with at least a 26-fold selectivity over CB1 receptors. Compound 25 behaved

  尽管它们的化学结构不同，delta9-四氢大麻酚（THC）和阿南酰胺（AEA）具有共同的药理特性。这项研究旨在寻找克服AEA及其类似物不稳定性的新型大麻素受体配体。为此，我们计划合成一系列化合物，这些化合物既保留了植物大麻素的刚性结构，又保留了类似于anandamide的柔性部分。对CB1和CB2受体，阿南酰胺膜转运蛋白（AMT）和脂肪酸酰胺水解酶（FAAH）的结合研究表明，一些新开发的化合物对大麻素CB1和CB2受体具有很高的亲和力和特异性。化合物25是有效的CB1和CB2配体，其亲和常数明显低于AEA，与WIN 55-212类似，化合物52是有效的CB2配体，尽管化合物对CB1受体的选择性不是很高，但化合物43是CB2配体，其选择性比CB1受体至少高26倍。化合物25在循环AMP功能试验中对CB1受体起反向激动剂的作用。